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Lymphatic platelet thrombosis inhibits fracture healing by decreased lymphatic transporting DAMPs in mice

ABSTRACT: Lymphatic vessels (LVs) interdigitated with blood vessels, travel and form an extensive transport network in the musculoskeletal system. Blood vessels in bone regulate osteogenesis and hematopoiesis, however, whether LVs in bone affect fracture healing is unclear. Here, by near infrared indocyanine green lymphatic imaging (NIR-ICG), we examined lymphatic drainage function at the tibial fracture sites and found lymphatic drainage insufficiency (LDI) occurred as early as two weeks after fracture. Sufficient lymphatic drainage facilitates fracture healing. In addition, we identified that lymphatic platelet thrombosis (LPT) blocks the draining lymphoid sinus and LVs, caused LDI and then inhibited fracture healing, which can be rescued by a pharmacological approach. Moreover, unblocked lymphatic drainage inhibits neutrophils influx and induce M2-like macrophages palarization of hematoma niche to support osteoblast (OB) survival and bone marrow-derived mesenchymal stem cell (BMSC) proliferation via transporting damage-associated molecular patterns (DAMPs). These findings demonstrate that LPT limits fracture healing by blocking lymphatic drainage from transporting DAMPs. Together, these findings represent a novel way forward in the treatment of bone fracture healing.

ORGANISM(S): Rattus Norvegicus

SUBMITTER: Yongjun Wang

PROVIDER: PXD044917 | iProX | Mon Aug 28 00:00:00 BST 2023

REPOSITORIES: iProX

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Lymphatic platelet thrombosis limits bone repair by precluding lymphatic transporting DAMPs

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